Disulfiram (Antabuse®; 1,1′,1″,1′″-[disulfanediylbis(carbonothioylnitrilo)] tetraethane) when combined with metal ions has been shown to effectively kill a wide variety of cancer cells at the concentration of sub-micromolar level while not affecting normal cells. Specifically, it is believed that when disulfiram combines with metals (dithiocarbamate complexes), it can function as a proteasome inhibitor. Clinical trials have been instigated to examine effectiveness of disulfiram complexed with copper gluconate against liver cancer and of disulfiram as adjuvant against lung cancer. Unfortunately, the application of disulfiram is limited due to its extremely low bioavailability and short half-life, as well as undesirable side effects such as headache, decreased sexual ability in males, skin rash, and mood change.
To advance application of anticancer drugs, various approaches have been explored toward improvement of targeting of the anticancer drugs and decrease of side-effects. For instance, expression level difference of specific receptors on normal and cancer cells have been examined for targeting as well as unique physiological properties of tumors such as low pH, high glutathione (GSH) levels, and abnormal metal ion concentrations. Elevated copper concentration (up to 2-3 fold) has been observed in a wide spectrum of tumors including ovarian, breast, cervical, prostate, and leukemia and this has suggested targeted approaches using chelators in cancer treatment. While such approaches have provided improvement in the art, room for further improvement exists.
What are needed in the art are materials and methods that can effectively deliver active forms of disulfiram to cancer cells for effective eradication while preventing damage to healthy tissue.